Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 191, Issue -, Pages 59-65Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.08.032
Keywords
Caenorhabditis elegans; High-throughput screen; U; S; EPA ToxCast screening library; Oxidative stress
Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- U.S. Environmental Protection Agency, Office of Research and Development
- NSERC Discovery Grant [04486]
- Canada Foundation for Innova-tion John R. Evans Leaders Fund [40325]
- WCVM
- Centre of Computational Toxicology and Exposure
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This study used C. elegans as a model organism to screen and identify chemicals that induce oxidative stress, and identified 49 such chemicals.
The metabolism of xenobiotic chemicals from the environment can produce reactive oxygen species leading to oxidative stress that is detrimental to the cell. To study the environmental factors that influence oxidative stress, we employed C. elegans engineered with a GFP tagged to the glutathione s-transferase 4 gene encoding a phase II enzyme as a biomarker for oxidative stress to screen against the U.S. EPA Toxcast library containing 4665 unique chemicals. We identified 49 chemicals that induced oxidative stress, as indicated by an increase in gst-4p::GFP signal. Quantitative PCR was used to measure the changes in mRNA expression corresponding to phase II detoxification enzymes to confirm the induction of oxidative stress for the top 10 chemicals. Among these chemicals include pesticides such as tepraloxydim, dichlone, pentachloronitrobenzene, and common industrial reagents such as ethyl acrylate and dinitrochlorobenzene. Overall, this study presents a comprehensive screening and identification of environmentally relevant chemicals that pose potential cellular toxicity as inducers of oxidative stress.
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